Preformulation Investigation I: Relation of Salt Forms and Biological Activity of an Experimental Antihypertensive

The Utility of Sulfonate Salts in Drug Development

“…8 The driving force for this reaction is the generation of volatile hydrogen chloride gas that is either lost from the system or reacts with other components of the formulation/processing equipment leading to either de-stabilization and/or processing issues. 35,36 Narurkar et al 37 reported on the rusting of tablet tooling which was attributed to the liberation of hydrogen chloride gas from the hydrochloride salt of the API. A similar phenomenon also occurs during lyophilization where the high vacuum/low temperature combination tends to drive off labile hydrogen chloride gas from the corresponding hydrochloride salts.…”

Absorption and Physicochemical Properties of the NCE

“…However, enhanced salt solubility may not guarantee better in vivo absorption [66][67][68]. When a salt or pH-adjusted formulation is used, the degree of bioavailability improvement may be largely dependent on the degree of supersaturation with respect to the equilibrium solubility in GI tract [69,70].…”

Incorporation of Physiologically Based Pharmacokinetic Modeling in the Evaluation of Solubility Requirements for the Salt Selection Process: A Case Study Using Phenytoin

“…Formulation-based approaches that improve both solubility and dissolution rate have been widely used in both preclinical and clinical studies to improve oral exposure. Approaches such as the use of pro-drugs, inclusion complexation, nanoparticles, co-solvents, micelles/emulsions, salts, co-crystals, and amorphous solids to deliver poorly soluble compounds orally have been widely reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”